Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation—Family Case Report and Review of the Literature
PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), that mainly presents with ventricular pre-excitation, cardiac hypertrophy and progressive conduction system degeneration. Its natural course, treatment and prognosis are signific...
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MDPI AG
2022-12-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/12/2136 |
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| author | Andreea Sorina Marcu Radu Vătăşescu Sebastian Onciul Viorica Rădoi Ruxandra Jurcuţ |
| author_facet | Andreea Sorina Marcu Radu Vătăşescu Sebastian Onciul Viorica Rădoi Ruxandra Jurcuţ |
| author_sort | Andreea Sorina Marcu |
| collection | DOAJ |
| description | PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), that mainly presents with ventricular pre-excitation, cardiac hypertrophy and progressive conduction system degeneration. Its natural course, treatment and prognosis are significantly different from sarcomeric HCM. The clinical phenotypes of PRKAG2 syndrome often overlap with HCM due to sarcomere protein mutations, causing this condition to be frequently misdiagnosed. The syndrome is caused by mutations in the gene encoding for the γ2 regulatory subunit (<i>PRKAG2</i>) of 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK), an enzyme that modulates glucose uptake and glycolysis. <i>PRKAG2</i> mutations (OMIM#602743) are responsible for structural changes of AMPK, leading to an impaired myocyte glucidic uptake, and finally causing storage cardiomyopathy. We describe the clinical and investigative findings in a family with several affected members (NM_016203.4:c.905G>A or p.(Arg302Gln), heterozygous), highlighting the various phenotypes even in the same family, and the utility of genetic testing in diagnosing PS. The particularity of this family case is represented by the fact that the index patient was diagnosed at age 16 with cardiac hypertrophy and ventricular pre-excitation while his mother, by age 42, only had Wolff–Parkinson–White syndrome, without left ventricle hypertrophy. Both the grandmother and the great-grandmother underwent pacemaker implantation at a young age because of conduction abnormalities. Making the distinction between PS and sarcomeric HCM is actionable, given the early-onset of the disease, the numerous life-threatening consequences and the high rate of conduction disorders. In patients who exhibit cardiac hypertrophy coexisting with ventricular pre-excitation, genetic screening for <i>PRKAG2</i> mutations should be considered. |
| first_indexed | 2024-03-09T16:10:36Z |
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| language | English |
| last_indexed | 2024-03-09T16:10:36Z |
| publishDate | 2022-12-01 |
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| record_format | Article |
| series | Life |
| spelling | doaj.art-0873909ee7674e1d824938cc996729132023-11-24T16:14:10ZengMDPI AGLife2075-17292022-12-011212213610.3390/life12122136Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation—Family Case Report and Review of the LiteratureAndreea Sorina Marcu0Radu Vătăşescu1Sebastian Onciul2Viorica Rădoi3Ruxandra Jurcuţ4Expert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, RomaniaCardiology Department, Emergency Clinical Hospital Floreasca, 8 Calea Floreasca, 014461 Bucharest, RomaniaCardiology Department, Emergency Clinical Hospital Floreasca, 8 Calea Floreasca, 014461 Bucharest, RomaniaDepartment of Medical Genetics, University of Medicine and Pharmacy Carol Davila, 8 Eroii Sanitari Blvd., 050474 Bucharest, RomaniaExpert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, RomaniaPRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), that mainly presents with ventricular pre-excitation, cardiac hypertrophy and progressive conduction system degeneration. Its natural course, treatment and prognosis are significantly different from sarcomeric HCM. The clinical phenotypes of PRKAG2 syndrome often overlap with HCM due to sarcomere protein mutations, causing this condition to be frequently misdiagnosed. The syndrome is caused by mutations in the gene encoding for the γ2 regulatory subunit (<i>PRKAG2</i>) of 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK), an enzyme that modulates glucose uptake and glycolysis. <i>PRKAG2</i> mutations (OMIM#602743) are responsible for structural changes of AMPK, leading to an impaired myocyte glucidic uptake, and finally causing storage cardiomyopathy. We describe the clinical and investigative findings in a family with several affected members (NM_016203.4:c.905G>A or p.(Arg302Gln), heterozygous), highlighting the various phenotypes even in the same family, and the utility of genetic testing in diagnosing PS. The particularity of this family case is represented by the fact that the index patient was diagnosed at age 16 with cardiac hypertrophy and ventricular pre-excitation while his mother, by age 42, only had Wolff–Parkinson–White syndrome, without left ventricle hypertrophy. Both the grandmother and the great-grandmother underwent pacemaker implantation at a young age because of conduction abnormalities. Making the distinction between PS and sarcomeric HCM is actionable, given the early-onset of the disease, the numerous life-threatening consequences and the high rate of conduction disorders. In patients who exhibit cardiac hypertrophy coexisting with ventricular pre-excitation, genetic screening for <i>PRKAG2</i> mutations should be considered.https://www.mdpi.com/2075-1729/12/12/2136hypertrophic cardiomyopathygenocopyPRKAG2Wolf–Parkinson–White syndrome |
| spellingShingle | Andreea Sorina Marcu Radu Vătăşescu Sebastian Onciul Viorica Rădoi Ruxandra Jurcuţ Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation—Family Case Report and Review of the Literature Life hypertrophic cardiomyopathy genocopy PRKAG2 Wolf–Parkinson–White syndrome |
| title | Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation—Family Case Report and Review of the Literature |
| title_full | Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation—Family Case Report and Review of the Literature |
| title_fullStr | Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation—Family Case Report and Review of the Literature |
| title_full_unstemmed | Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation—Family Case Report and Review of the Literature |
| title_short | Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation—Family Case Report and Review of the Literature |
| title_sort | intrafamilial phenotypical variability linked to prkag2 mutation family case report and review of the literature |
| topic | hypertrophic cardiomyopathy genocopy PRKAG2 Wolf–Parkinson–White syndrome |
| url | https://www.mdpi.com/2075-1729/12/12/2136 |
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